An Open-label, Single-arm Clinical Study to Evaluate the Safety and Preliminary Efficacy of OriV508 Injection in Treating Relapsed/Refractory Hematological Malignancies

NCT07101705 | Recruiting Early Phase 1

• 1 other identifier: OriV508-T1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, single arm, open-label, dose escalation, phase 1 study to evaluate the safety, tolerability, preliminary efficacy and immunogenicity of OriV508 injection for patients with relapsed/refractory hematological malignancies.

Conditions

Multiple Myeloma (MM); Non-Hodgkin Lymphoma (NHL)

Keywords

BCMA/CD19; multiple myeloma; Non-Hodgkin lymphoma; In vivo CAR-T

Outcome Measures

Primary Outcomes (4)

• Dose-limiting toxicities (DLTs)

  Dose-limiting toxicities (DLTs) are evaluated between the infusion and 28 days post-infusion.

• Cytokine release syndrome (CRS)

  Cytokine release syndrome (CRS) would be graded according to the ASTCT consensus.

  up to Day 28 post-infusion

• Immune cell-associated immune effector cell-associated neurotoxicity syndrome (ICANS)

  ICANS would be scored according to Immune Effector Cell-Associated Encephalopathy (ICE), and then graded by the ASTCT consensus.

  up to Day 28 post-infusion

• Treatment-associated adverse effects (AEs)

  All other AEs would be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).

  From the enrollment to up to the end of treatment at 96 weeks after treatment of OriV508 or withdrawal from the study

Secondary Outcomes (8)

• Overall response rate (ORR)

  From OriV508 infusion to the end of treatment at 96 weeks

• Complete response (CR) rate

  From OriV508 infusion to the end of treatment at 96 weeks

• Duration of response (DOR)

  From OriV508 infusion to the end of the treatment at 96 weeks

• Time to response (TTR)

  From OriV508 infusion to the end of treatment at 96 weeks

• Progression-free survival (PFS)

  From OriV508 infusion to the end of the treatment at 96 weeks

Other Outcomes (2)

• Immunogenicity of OriV508 injection

  up to 96 weeks post-infusion

• Replication competent lentivirus (RCL)

  Baseline, Week 12, Week 24, Week 48, Week 96 post-infusion or withdrawal from the study.

Study Arms (1)

OriV508 injection

EXPERIMENTAL

OriV508 injection is one kind of non-replicative self-inactivating lentivirus vector which carries an effective BCMA/CD19 dual-target CAR. OriV508 can be administered intravenously and produce BCMA/CD19 CAR-T in vivo.

Drug: OriV508 Injection

Interventions

OriV508 Injection DRUG

OriV508 injection is one kind of non-replicative self-inactivating lentivirus vector which carries an effective BCMA/CD19 dual-target CAR. OriV508 can be administered intravenously and produce BCMA/CD19 CAR-T in vivo.

Also known as: OriV508

OriV508 injection

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 - 75 years.
• ECOG scores 0-1.
• Expected survival time ≥ 12 weeks.
• Have a record of confirmed multiple myeloma (MM) according to IMWG criteria, or a record of histologically confirmed aggressive B-cell non-Hodgkin lymphoma (B-NHL). According to the definition of the 2022 World Health Organization (WHO) classification, the pathological types of aggressive B-NHL include: diffuse large B-cell lymphoma, not otherwise specified; diffuse large B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL2 rearrangements; high-grade B-cell lymphoma, not otherwise specified; primary mediastinal B-cell lymphoma; mantle cell lymphoma; grade 3b follicular lymphoma; large B-cell lymphoma transformed from indolent B-NHL.
• For MM subjects only: (1) Have received at least 2 lines of anti-tumor therapy, with each line of therapy undergoing at least one complete treatment cycle, and have experienced disease progression during or within 12 months after the last treatment; or be judged by the investigator as double-refractory to immunomodulators and proteasome inhibitors, and did not achieve a minimal response (MR) or better during the last treatment or experienced disease progression within 60 days after the end of treatment. (2) Have measurable lesions during the screening period, meeting any of the following criteria: (a) Serum M-protein ≥ 0.5 g/dL; (b) Urine M-protein≥ 200 mg/24h; (c) Involved free light chain (FLC) level ≥10 mg/dL provided serum FLC ratio is abnormal; (d) Plasma cell percentage ≥30% detected by bone marrow aspirate/biopsy; (e) Presence of at least one extramedullary lesion with a maximum diameter ≥ 2 cm.
• For aggressive B-NHL subjects only: (1) Have received at least 2 lines of anti-tumor therapy, and are refractory to the last line of therapy (at least 2 cycles) (best response is PD or SD) or have experienced disease progression after the end of treatment. Previous treatments must include standard treatment regimens with anti-CD20 monoclonal antibodies (except for subjects with CD20-negative tumors) and anthracyclines; (2) Have at least one measurable lesion during the screening period: lymph node lesions must have a longest diameter \> 1.5 cm, and extranodal lesions must have a longest diameter \> 1.0 cm.
• Hemogram meets the following requirements:
• Hemoglobin ≥ 6 g/dL (no red blood cell transfusion within 1 week prior to screening, recombinant human erythropoietin is permitted);
• Absolute neutrophil count (ANC) ≥ 750 /μL (no granulocyte colony-stimulating factor (G-CSF) used within 1 week prior to screening or no pegylated G-CSF used within 2 weeks prior to screening);
• Platelet count ≥ 50,000 /μL;
• Lymphocyte count ≥ 500 /μL.
• Renal function: Creatinine clearance (CrCl) (Modification of Diet in Renal Disease (MDRD) formula) ≥ 40 mL/min/1.73m² (for MM subjects with CrCl \< 40 mL/min/1.73m², the investigator can decide whether to enroll based on clinical indications).
• Liver function: Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3.0 × upper limit of normal (ULN), total bilirubin ≤ 1.5 × ULN (for subjects with Gilbert's syndrome or liver invasion by tumor, ALT and AST ≤ 5.0 × ULN and total bilirubin ≤ 3 × ULN are permitted).
• Cardiac function: Left ventricular ejection fraction ≥ 45%.
• Pulmonary function: Pulse oxygen saturation ≥ 92% without oxygen inhalation.

You may not qualify if:

• The subject has received the following therapy prior to signing the ICF:
• Small molecule targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least 5 half-lives, whichever is longer;
• Immunosuppressive agent therapy (such as tacrolimus, mycophenolate mofetil, etc.) within 28 days;
• Monoclonal antibody treatment within 21 days;
• Cytotoxic therapy within 14 days;
• Proteasome inhibitor therapy within 14 days;
• Immunomodulator agent therapy within 7 days;
• Therapeutic dose of corticosteroids (defined as prednisone ≥ 20 mg/day or equivalent dose of other corticosteroids) within 72 hours, but physiological replacement dose, topical and inhaled corticosteroids are permitted;
• Radiotherapy within 28 days (only for subjects whose radiation field covers \> 5% of bone marrow reserve).
• Received autologous hematopoietic stem cell transplantation within 24 weeks prior to signing the ICF.
• Received organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Have other malignant tumors prior to screening, except for the following cases: malignant tumors that have received radical treatment and have no known active disease within 2 years prior to screening; or adequately treated non-melanoma skin cancer with no evidence of active disease.
• Previously treated with any viral therapy using vesicular stomatitis virus G (VSVG)-pseudotyped virus.
• Known active central nervous system involvement or clinical signs of meningeal involvement.
• Complicated with severe uncontrolled active infections (bacterial, viral, fungal, etc.).

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• OriCell Therapeutics Co., Ltd.: collaborator

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Lymphatic Diseases

Study Officials

• Heng Mei, Ph.D&M.D

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heng Mei, Ph.D&M.D

CONTACT

027-8572600; hmei@hust.edu.cn

Jia Xu, Ph.D

CONTACT

+86 18274201261; xu_jia@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 28, 2025
• First Posted: August 3, 2025
• Study Start: September 8, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: September 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)